The effect of iron fortification of complementary foods on infant gut microbiota

说明（申请人提供）：婴儿和2岁以下的儿童是缺铁性贫血发病率最高的年龄组。向这一年龄组提供足够的膳食铁是一项挑战，使用微量营养素粉末在家庭补充食品中强化铁是一种很有前途的方法。然而，世卫组织建议，在证实其安全性之前，不要在疟疾地区无针对性地使用含有儿童铁RDA的单剂家庭微量营养素粉末。美国国立卫生研究院技术工作组（2009年）“在疟疾负担地区安全有效地使用铁干预措施的考虑因素”的研究重点包括：i)通过不同方式和配方输送铁对肠道菌群的影响；Ii)肠道内的铁在多大程度上有利于具有致病潜力的肠道微生物的生长。因此，我们计划通过体外和体内的互补研究来研究家庭强化铁对婴儿肠道微生物群的影响。重点是沙门氏菌，这是在严重疟疾菌血症研究中最常涉及的病原体。该研究的目的是：i)在体内，确定在腹泻病和疟疾高风险的肯尼亚婴儿中使用含铁微量营养素粉末的家庭强化是否会改变肠道微生物群的组成和代谢活性，从而有利于细菌肠道病原体的生长，并确定特异性

DESCRIPTION (provided by applicant): Infants and children < 2 yrs are the age group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron fortification of complementary foods using micronutrient powders is a promising approach. However, WHO has recommended against untargeted use of in-home micronutrient powders that contain the iron RDA for a child in a single dose in malarial areas, until their safety is proven. Research priorities from the U.S. NIH Technical Working Group (2009) "Considerations for the safe and effective use of iron interventions in areas of malaria burden" include: i) effect of iron delivered through different means and formulations on gut microflora; ii) extent to which iron in the gut lumen favors growth of enteric microorganisms with a pathogenic potential. Therefore, we plan to investigate the effect of iron provided in in-home fortification on the infant gut microbiome, using complementary in vitro and in vivo lines of investigation. The focus is on Salmonella spp., as the pathogen most often implicated in studies of bacteremia in severe malaria. The study aims are: i) in vivo, to determine if in-home fortification using an iron-containing micronutrient powder in Kenyan infants at high risk for diarrheal disease and malaria will modify the composition and metabolic activity of the gut microbiota to favor growth of bacterial enteropathogens, and identify the specific enteropathogens that emerge; ii) in vitro, using immobilized infant fecal microflora in a continuous colonic fermentation model inoculated with the specific pathogens identified in the in vivo studies, as well as a cell culture Salmonella infection model, to determine the mechanisms by which colonic iron selects for bacterial enteropathogens, including iron dose, iron form and the molecular and metabolic response of the gut microbiota to iron. To thoroughly characterize the global impact of iron fortification on the gut microbiota and specifically, on enteropathogens, we will apply TTGE, POR, high-throughput 16S rRNA gene sequence analysis, SCFA production by HPLC as well as metagenomic approaches to measure genotype effects. PUBLIC HEALTH RELEVANCE: This project should provide basic knowledge on the interactions between dietary iron and the infant gut microbiota in order to design safe and effective in-home fortification strategies to control iron deficiency anemia in infants in tropical countries with high burdens of infectious disease.